Characterization of SSR103800, a selective inhibitor of the glycine transporter-1 in models predictive of therapeutic activity in schizophrenia☆
| Autor: | Bruno Biton, Guy Griebel, Caroline Cohen, Pascal George, Philippe Pichat, Mireille Sevrin, Genevieve Estenne-Bouhtou, Nancy Rogacki, C. Desvignes, Bernard Scatton, Patrick Avenet, Xavier Vigé, Jeanne Stemmelin, Olivier Bergis, Annick Coste, Denis Boulay, Christophe Lanneau, Jean Paul Terranova, Régis Steinberg, R. Alonso, Gihad Dargazanli, F. Oury-Donat |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Reflex Startle medicine.medical_specialty N-Methylaspartate Clinical Biochemistry Glycine Phencyclidine Motor Activity Hippocampal formation Toxicology Biochemistry Mice Behavioral Neuroscience Discrimination Psychological Glycine Plasma Membrane Transport Proteins Internal medicine Moro reflex medicine Extracellular Animals Swimming Biological Psychiatry Prepulse inhibition Pharmacology biology Chemistry Excitatory Postsynaptic Potentials Recognition Psychology Stereoisomerism Antidepressive Agents Endocrinology Glycine transporter 1 Anesthesia Schizophrenia Reflex biology.protein Excitatory postsynaptic potential Antidepressant Dizocilpine Maleate Extracellular Space Gerbillinae Excitatory Amino Acid Antagonists Antipsychotic Agents |
| Zdroj: | Pharmacology Biochemistry and Behavior. 91:47-58 |
| ISSN: | 0091-3057 |
| Popis: | On native human, rat and mouse glycine transporter-1(GlyT1), SSR130800 behaves as a selective inhibitor with IC50 values of 1.9, 5.3 and 6.8 nM, respectively. It reversibly blocked glycine uptake in mouse brain cortical homogenates, increased extracellular levels of glycine in the rat prefrontal cortex, and potentiated NMDA-mediated excitatory postsynaptic currents in rat hippocampal slices. SSR103800 (30 mg/kg, p.o.) decreased MK-801- and PCP-induced locomotor hyperactivity in rodents. SSR103800 (1 and 10 mg/kg, p.o.) attenuated social recognition deficit in adult rats induced by neonatal injections of PCP (10 mg/kg, s.c., on post-natal day 7, 9 and 11). SSR103800 (3 mg/kg, p.o.) counteracted the deficit in short-term visual episodic-like memory induced by a low challenge dose of PCP (1 mg/kg, i.p.), in PCP-sensitized rats (10 mg/kg, i.p.). SSR103800 (30 mg/kg, i.p.) increased the prepulse inhibition of the startle reflex in DBA/1J mice. SSR103800 decreased defensive- and despair-related behaviors in the tonic immobility test in gerbils (10 and 30 mg/kg, p.o.) and in the forced-swimming procedure in rats (1 and 3 mg/kg, p.o.), respectively. These findings suggest that SSR103800 may have a therapeutic potential in the management of the core symptoms of schizophrenia and comorbid depression states. |
| Databáze: | OpenAIRE |
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